P98174 (FGD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
FYVE, RhoGEF and PH domain-containing protein 1

Alternative name(s):
Faciogenital dysplasia 1 protein
Rho/Rac guanine nucleotide exchange factor FGD1
Short name=Rho/Rac GEF
Zinc finger FYVE domain-containing protein 3

Gene names

Name:	FGD1
Synonyms:	FGDY, ZFYVE3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	961 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Ref.5
Subunit structure	Interacts with DBNL/ABP1 and CTTN. May interact with CCPG1 By similarity. Binds CDC42.
Subcellular location	Cytoplasm By similarity. Cell projection › lamellipodium By similarity. Cell projection › ruffle By similarity. Cytoplasm › cytoskeleton By similarity. Note: Associated with membrane ruffles and lamellipodia By similarity.
Tissue specificity	Expressed in fetal heart, brain, lung, kidney and placenta. Less expressed in liver; adult heart, brain, lung, pancreas and skeletal muscle.
Domain	The DH domain is involved in interaction with CCPG1 By similarity.
Involvement in disease	Aarskog-Scott syndrome (AAS) [MIM:305400]: A rare multisystemic disorder characterized by disproportionately short stature, and by facial, skeletaland urogenital anomalies. Some patients manifest mental retardation, attention deficit disorder and hyperactivity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.12 Defects in FGD1 are found in a pateint with non-syndromal X-linked mental retardation.
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 FYVE-type zinc finger. Contains 2 PH domains.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Cytoskeleton
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB apoptotic process Traceable author statement. Source: Reactome filopodium assembly Inferred from direct assay Ref.5. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome organ morphogenesis Traceable author statement Ref.1. Source: ProtInc regulation of Cdc42 GTPase activity Inferred from direct assay Ref.5. Source: UniProtKB regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA ruffle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.5. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro small GTPase binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 961	961	FYVE, RhoGEF and PH domain-containing protein 1		PRO_0000080940
Regions
	Domain	373 – 561	189	DH
	Domain	590 – 689	100	PH 1
	Domain	821 – 921	101	PH 2
	Zinc finger	730 – 790	61	FYVE-type
	Motif	171 – 187	17	SH3-binding Potential
	Compositional bias	7 – 330	324	Pro-rich
Amino acid modifications
	Modified residue	48	1	Phosphoserine Ref.6
	Modified residue	205	1	Phosphoserine Ref.6
	Modified residue	365	1	Phosphoserine Ref.8
	Modified residue	711	1	Phosphothreonine Ref.6
	Modified residue	715	1	Phosphoserine Ref.6
Natural variations
	Natural variant	205	1	S → I in AAS. Ref.12		VAR_019268
	Natural variant	312	1	P → L in non-syndromal X-linked mental retardation. Ref.11 Corresponds to variant rs28935498 [ dbSNP | Ensembl ].		VAR_019269
	Natural variant	380	1	E → A in AAS. Ref.12		VAR_019270
	Natural variant	443	1	R → H in AAS. Ref.12		VAR_019271
	Natural variant	522	1	R → H in AAS. Ref.9		VAR_015236
	Natural variant	610	1	R → Q in AAS. Ref.10 Corresponds to variant rs28935497 [ dbSNP | Ensembl ].		VAR_015237
Experimental info
	Sequence conflict	10 – 23	14	AGPSE…ATNPP → RRAFGARTPGHEPA Ref.1
	Sequence conflict	195	1	A → G in AAA57004. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P98174 [UniParc]. Last modified February 1, 2003. Version 2. Checksum: 30963F7B9931E45C	FASTA	961	106,561
	10 20 30 40 50 60 MHGHRAPGGA GPSEPEHPAT NPPGAAPPAC ADSDPGASEP GLLARRGSGS ALGGPLDPQF 70 80 90 100 110 120 VGPSDTSLGA APGHRVLPCG PSPQHHRALR FSYHLEGSQP RPGLHQGNRI LVKSLSLDPG 130 140 150 160 170 180 QSLEPHPEGP QRLRSDPGPP TETPSQRPSP LKRAPGPKPQ VPPKPSYLQM PRMPPPLEPI 190 200 210 220 230 240 PPPPSRPLPA DPRVAKGLAP RAEASPSSAA VSSLIEKFER EPVIVASDRP VPGPSPGPPE 250 260 270 280 290 300 PVMLPQPTSQ PPVPQLPEGE ASRCLFLLAP GPRDGEKVPN RDSGIDSISS PSNSEETCFV 310 320 330 340 350 360 SDDGPPSHSL CPGPPALASV PVALADPHRP GSQEVDSDLE EEDDEEEEEE KDREIPVPLM 370 380 390 400 410 420 ERQESVELTV QQKVFHIANE LLQTEKAYVS RLHLLDQVFC ARLLEEARNR SSFPADVVHG 430 440 450 460 470 480 IFSNICSIYC FHQQFLLPEL EKRMEEWDRY PRIGDILQKL APFLKMYGEY VKNFDRAVEL 490 500 510 520 530 540 VNTWTERSTQ FKVIIHEVQK EEACGNLTLQ HHMLEPVQRI PRYELLLKDY LLKLPHGSPD 550 560 570 580 590 600 SKDAQKSLEL IATAAEHSNA AIRKMERMHK LLKVYELLGG EEDIVSPTKE LIKEGHILKL 610 620 630 640 650 660 SAKNGTTQDR YLILFNDRLL YCVPRLRLLG QKFSVRARID VDGMELKESS NLNLPRTFLV 670 680 690 700 710 720 SGKQRSLELQ ARTEEEKKDW VQAINSTLLK HEQTLETFKL LNSTNREDED TPPNSPNVDL 730 740 750 760 770 780 GKRAPTPIRE KEVTMCMRCQ EPFNSITKRR HHCKACGHVV CGKCSEFRAR LVYDNNRSNR 790 800 810 820 830 840 VCTDCYVALH GVPGSSPACS QHTPQRRRSI LEKQASVAAE NSVICSFLHY MEKGGKGWHK 850 860 870 880 890 900 AWFVVPENEP LVLYIYGAPQ DVKAQRSLPL IGFEVGPPEA GERPDRRHVF KITQSHLSWY 910 920 930 940 950 960 FSPETEELQR RWMAVLGRAG RGDTFCPGPT LSEDREMEEA PVAALGATAE PPESPQTRDK T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor." Pasteris N.G., Cadle A., Logie L.J., Porteous M.E.M., Schwartz C.E., Stevenson R.E., Glover T.W., Wilroy R.S., Gorski J.L. Cell 79:669-678(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Craniofacial.
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"The faciogenital dysplasia gene product FGD1 functions as a Cdc42Hs-specific guanine-nucleotide exchange factor." Zheng Y., Fischer D.J., Santos M.F., Tigyi G., Pasteris N.G., Gorski J.L., Xu Y. J. Biol. Chem. 271:33169-33172(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-205; THR-711 AND SER-715, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, MASS SPECTROMETRY.
[9]	"Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome." Schwartz C.E., Gillessen-Kaesbach G., May M., Cappa M., Gorski J.L., Steindl K., Neri G. Eur. J. Hum. Genet. 8:869-874(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AAS HIS-522.
[10]	"A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome)." Orrico A., Galli L., Falciani M., Bracci M., Cavaliere M.L., Rinaldi M.M., Musacchio A., Sorrentino V. FEBS Lett. 478:216-220(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AAS GLN-610.
[11]	"Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene." Lebel R.R., May M., Pouls S., Lubs H.A., Stevenson R.E., Schwartz C.E. Clin. Genet. 61:139-145(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NONSYNDROMAL X-LINKED MENTAL RETARDATION LEU-312.
[12]	"Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients." Orrico A., Galli L., Cavaliere M.L., Garavelli L., Fryns J.-P., Crushell E., Rinaldi M.M., Medeira A., Sorrentino V. Eur. J. Hum. Genet. 12:16-23(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AAS ILE-205; ALA-380 AND HIS-443.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U11690 mRNA. Translation: AAA57004.1. Z85987 Genomic DNA. Translation: CAI42222.1. CH471154 Genomic DNA. Translation: EAW93179.1. BC034530 mRNA. Translation: AAH34530.1.
IPI	IPI00024312.
PIR	A55380.
RefSeq	NP_004454.2. NM_004463.2.
UniGene	Hs.709201.
3D structure databases
ProteinModelPortal	P98174.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000364277.
PTM databases
PhosphoSite	P98174.
Polymorphism databases
DMDM	28202247.
Proteomic databases
PaxDb	P98174.
PRIDE	P98174.
Protocols and materials databases
DNASU	2245.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375135; ENSP00000364277; ENSG00000102302.
GeneID	2245.
KEGG	hsa:2245.
UCSC	uc004dtg.3. human.
Organism-specific databases
CTD	2245.
GeneCards	GC0XM054488.
HGNC	HGNC:3663. FGD1.
HPA	HPA000911.
MIM	300546. gene. 305400. phenotype.
neXtProt	NX_P98174.
Orphanet	915. Aarskog-Scott syndrome.
PharmGKB	PA28102.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295069.
HOGENOM	HOG000220866.
HOVERGEN	HBG007506.
InParanoid	P98174.
KO	K05720.
OMA	DDGPPSH.
OrthoDB	EOG4PK274.
PhylomeDB	P98174.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P98174.
CleanEx	HS_FGD1.
Genevestigator	P98174.
GermOnline	ENSG00000102302. Homo sapiens.
Family and domain databases
Gene3D	1.20.900.10. 1 hit. 2.30.29.30. 2 hits. 3.30.40.10. 1 hit.
InterPro	IPR000219. DH-domain. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR000306. Znf_FYVE. IPR017455. Znf_FYVE-rel. IPR011011. Znf_FYVE_PHD. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF01363. FYVE. 1 hit. PF00169. PH. 2 hits. PF00621. RhoGEF. 1 hit. [Graphical view]
SMART	SM00064. FYVE. 1 hit. SM00233. PH. 2 hits. SM00325. RhoGEF. 1 hit. [Graphical view]
SUPFAM	SSF48065. DH-domain. 1 hit. SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS00741. DH_1. False negative. PS50010. DH_2. 1 hit. PS50003. PH_DOMAIN. 2 hits. PS50178. ZF_FYVE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P98174.
ChEMBL	CHEMBL2862.
ChiTaRS	FGD1. human.
GenomeRNAi	2245.
NextBio	9083.
SOURCE	Search...

Entry information

Entry name

FGD1_HUMAN

Accession

Primary (citable) accession number: P98174
Secondary accession number(s): Q5H999, Q8N4D9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 1, 2003
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.